Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain.
Virology. 2013 Sep;444(1-2):274-81. doi: 10.1016/j.virol.2013.06.023. Epub 2013 Jul 21.
During the human immunodeficiency virus type 1 (HIV-1) pandemic, continuous, extensive genetic diversification of the virus has been observed. To study the effect of HIV-1 diversification on integrase-associated viral replication capacity (RC), 94 HIV-1 subtype B integrase sequences from two groups of antiretroviral-naive viruses isolated 15 y apart were amplified and recombined with an HIV-1 infectious clone. Viral RC was determined by infecting a T cell line with a long terminal repeat-driven green fluorescent protein reporter. Significant differences in integrase-mediated RC were observed between recombinant viruses from early and late isolates (p=0.0286). Integrases from late isolates had significantly lower sequence conservation scores compared to an ancestral subtype B sequence (p<0.0001). Integrase amino acid polymorphisms S17N, I72V, S119P, and D256E were associated with a lower ex vivo viral RC. These results suggest that integrase sequence diversification has affected ex vivo HIV-1 RC.
在人类免疫缺陷病毒 1 型（HIV-1）大流行期间，观察到病毒持续广泛的遗传多样化。为了研究 HIV-1 多样化对整合酶相关病毒复制能力（RC）的影响，扩增并重组了来自两个组的 94 个 HIV-1 亚型 B 整合酶序列，这两组抗逆转录病毒初治病毒相隔 15 年分离。通过用长末端重复驱动的绿色荧光蛋白报告基因感染 T 细胞系来确定病毒 RC。早期和晚期分离物的重组病毒之间观察到整合酶介导的 RC 存在显著差异（p=0.0286）。与原始亚型 B 序列相比，晚期分离物的整合酶序列保守性评分显著降低（p<0.0001）。整合酶氨基酸多态性 S17N、I72V、S119P 和 D256E 与体外病毒 RC 降低相关。这些结果表明，整合酶序列多样化已经影响了体外 HIV-1 RC。
